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ZusammenfassungDie COVID-19-Pandemie beeinflusst das Leben von Patient*innen mit chronisch-entzündlichen Darmerkrankungen (CED) in erheblicher Weise. Betroffene und Angehörige haben zahlreiche Fragen zum Erkrankungsrisiko, zum Verlauf einer möglichen SARS-CoV-2-Infektion oder auch zum Einfluss der CED-spezifischen Therapie. Auch bestehen bei vielen CED-Patient*innen zusätzliche Fragen zu Sicherheit und Wirksamkeit einer Impfung gegen SARS-CoV-2. Ziel dieser Übersicht ist die Zusammenfassung der neusten Erkenntnisse zu COVID-19 und CED, aber auch die Diskussion zum Impfansprechen (humoral/zellulär), zum Einfluss laufender Therapie auf die Impfantwort sowie zur Häufigkeit von Nebenwirkungen und zur Bedeutung der Booster-Immunisierungen zu führen und für das Gespräch mit Patient*innen eine Evidenz-basierte Grundlage zu schaffen.

Um die Versorgung von Patienten mit chronisch entzundlichen Darmerkrankungen (CED) in der COVID-19-Pandemie zu verbessern, wurden die aktuell gultigen Leitlinien der Deutschen Gesellschaft fur Gastroenterologie, Verdauungs- und Stoffwechselerkrankungen (DGVS) zum Morbus Crohn und der Colitis ulcerosa im Rahmen einer virtuellen Konferenz um aktuelle und praxisnahe Empfehlungen erweitert. Das Addendum adressiert insbesondere das Risiko fur eine COVID-19-Erkrankung bei Patienten mit CED, die Diagnostik unter den Bedingungen der Pandemie, die Konsequenzen fur die medikamentose und operative Therapie der Grunderkrankung sowie allgemeine Masnahmen zum Schutz vor Infektionen und fur eine Begleittherapie bei CED-Patienten.

The COVID-19 pandemic is significantly affecting the lives of patients with inflammatory bowel disease (IBD). Those affected and their relatives have numerous questions about the risk of the disease, the course of a possible SARS-CoV-2 infection or the influence of CED-specific therapy on these. Many IBD patients also have additional questions about the safety and effectiveness of a vaccination against SARS-CoV-2. The aim of this review is to summarize the latest findings on COVID-19 and IBD, but also to discuss vaccine response (humoral/cellular), the influence of ongoing therapy on the vaccine response as well as the frequency of side effects and the importance of booster immunizations and to create an evidence-based basis for discussion with patients.Die COVID-19-Pandemie beeinflusst das Leben von Patient*innen mit chronisch-entzündlichen Darmerkrankungen (CED) in erheblicher Weise. Betroffene und Angehörige haben zahlreiche Fragen zum Erkrankungsrisiko, zum Verlauf einer möglichen SARS-CoV-2-Infektion oder auch zum Einfluss der CED-spezifischen Therapie. Auch bestehen bei vielen CED-Patient*innen zusätzliche Fragen zu Sicherheit und Wirksamkeit einer Impfung gegen SARS-CoV-2. Ziel dieser Übersicht ist die Zusammenfassung der neusten Erkenntnisse zu COVID-19 und CED, aber auch die Diskussion zum Impfansprechen (humoral/zellulär), zum Einfluss laufender Therapie auf die Impfantwort sowie zur Häufigkeit von Nebenwirkungen und zur Bedeutung der Booster-Immunisierungen zu führen und für das Gespräch mit Patient*innen eine Evidenz-basierte Grundlage zu schaffen.

The influence of a SARS-CoV-2 infection on inflammatory bowel disease (IBD) has not yet been well characterized and it is unclear whether this requires an adaptation of the immunosuppressive therapy.A national register was established for the retrospective documentation of clinical parameters and changes in immunosuppressive therapy in SARS-CoV-2 infected IBD patients.In total, only 3 of 185 IBD patients (1.6 %) were tested for SARS-CoV-2 infection because of abdominal symptoms. In the course of COVID-19 disease, 43.5 % developed diarrhea, abdominal pain or hematochezia (risk of hospitalization with vs. without abdominal symptoms: 20.0 % vs. 10.6 %, p 0.01). With active IBD at the time of SARS-CoV-2 detection, there was an increased risk of hospitalization (remission 11.2 %, active IBD 23.3 % p 0.05). IBD-specific therapy remained unchanged in 115 patients (71.4 %); the most common change was an interruption of systemic therapy (16.2 %).New abdominal symptoms often appeared in SARS-CoV-2 infected IBD patients. However, these only rarely led to SARS-CoV-2 testing. A high IBD activity at the time of SARS-CoV-2 detection was associated with an increased risk of hospitalization.Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert.Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert.Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p 0,01). Bei aktiver CED zum Zeitpunkt des SARS-CoV-2-Nachweises bestand ein erhöhtes Hospitalisierungsrisiko (Remission 11,2 %, aktive CED 23,3 % p 0,05). Die CED-spezifische Therapie blieb bei 115 Patienten (71,4 %) unverändert; die häufigste Änderung bestand in einer Unterbrechung der systemischen Therapie (16,2 %).Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with significant morbidity and mortality. Although the precise cause remains unknown, disturbances in the intestinal microbial community have been linked to its pathogenesis. Randomized controlled trials in UC and relapsing Clostridioides difficile infection (CDI) have established fecal microbiota (FM) transfer (FMT) as an effective therapy. In this context, preliminary results indicated that the transfer of sterile fecal microbiota filtrates (0.2 μm; FMF, FMFT) of donor stool also drives gastrointestinal microbiota changes and eliminates symptoms in CDI patients. However, along with the success of FMT, regulatory agencies issued safety alerts following reports of serious adverse events due to transmission of enteric pathogens through FMT. To reduce this risk, we established an extensive test protocol for our donors and quarantine regulations for the produced capsules, but alternative concepts are desirable.Our project is a randomized, controlled, longitudinal, prospective, three-arm, multicenter, double-blind study to determine the safety and efficacy of repeated long-term, multi-donor FM or FMF transfers compared to placebo using oral, frozen capsules in 174 randomized patients with mild to moderate active UC. The primary outcome will be clinical remission at week 12.This proposal aims to examine (a) the efficacy of encapsulated transfer of FM and FMF as a therapy for mild to moderate UC, (b) the short- and long-term safety of FMT and FMFT in patients with UC, and (c) the microbial and immunologic changes that occur after FMT and FMFT to help understand how and why it affects inflammatory bowel disease.ClinicalTrials.gov NCT03843385 . DRKS (Deutsches Register für Klinische Studien) DRKS00020471.

Refractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management.Die Refraktäre Zöliakie (RCD) stellt eine seltene Komplikation der Zöliakie dar. Hier kommt es trotz einer strikten glutenfreien Diät zu einem Malabsorptionssyndrom auf der Basis einer Enteropathie mit Dünndarm-Zottenatrophie und -Kryptenhyperplasie. Unterteilt wird die RCD in einen autoimmunen Phänotyp (RCD Typ I) und ein Prä-Lymphom (RCD Typ II). Um die Versorgungsrealität im Umgang mit dieser Erkrankung in Deutschland abzubilden, erfolgte anhand eines eigens dafür entwickelten Fragebogens die Etablierung eines nationalen Registers. Zwischen 2014 und 2020 wurden insgesamt 53 Patienten gemeldet, bei denen in 46 Fällen (87%) die Diagnose RCD bestätigt werden konnte. Hierbei handelte es sich um 27 Patienten (59%) mit einer RCD Typ I und 19 Patienten (41%) mit einer RCD Typ II. Es zeigte sich ein breites Spektrum zur Anwendung kommender diagnostischer und therapeutischer Maßnahmen. Therapeutisch wurde unabhängig vom Subtyp bei 59% der RCD-Patienten Budesonid eingesetzt. Eine Ernährungstherapie erfolgte nur bei 5 Patienten (11%). Die Mortalität lag insgesamt bei 26% (12 Patienten) mit einer deutlichen Dominanz der Patienten mit einer RCD Typ II (9 Patienten, 47%). Zusammenfassend muss die RCD stärker in den Fokus nationaler Leitlinien gerückt werden, um deren Bekanntheitsgrad zu steigern, Standards zu etablieren und es so dem behandelnden Arzt zu ermöglichen, zeitnah die korrekte Diagnose zu stellen. Bei der Behandlung solcher Patienten muss aufgrund der Seltenheit der Erkrankung einmal mehr der Kontakt zu einem spezialisierten Zentrum empfohlen werden.

Zusammenfassung Einleitung Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert. Methodik Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert. Ergebnisse Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p Diskussion Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has influenced the lives of people worldwide Little is known about the effects of the COVID-19 pandemic on the behavior and fears of pediatric patients with inflammatory bowel disease (IBD) and their families We conducted a survey to determine the COVID-19 exposure, related perceptions, and information sources;medication compliance;and patients' and parents' behaviors, fears, and physician contact Methods: An anonymous cross-sectional survey of pediatric patients with IBD and their parents at one pediatric gastroenterology unit of a university medical center was performed Results: A total of 46 pediatric patients with IBD and 44 parents completed the survey Parents of pediatric patients with IBD had high fear of their children becoming infected with severe acute respiratory syndrome coronavirus 2 They perceived schools as the most hazardous environment, whereas the children did not Half the pediatric patients with IBD feared infection Patients and parents felt sufficiently informed about COVID-19 The primary source of guidance for pediatric patients was their parents (43%), followed by television and social media, whereas the parents mainly consulted internet news websites (52 2%), television, and public health institutes Pediatric patients with IBD adhered to their prescribed medication They also showed cautious behavior by enhancing hand hygiene (84%) and leaving the house less frequently than before However, in-person medical visits remained favored over video consultations Conclusion: Although parents expressed overprotective concerns, both parents and pediatric patients with IBD are coping well with the COVID-19 pandemic IBD-relevant information should be actively conveyed [ABSTRACT FROM AUTHOR] Copyright of Pediatric Gastroenterology, Hepatology & Nutrition is the property of Korean Society of Pediatric Gastroenterology, Hepatology & Nutrition and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Background: Fecal microbiota transfer (FMT) is increasingly being used in Germany, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. Methods: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. Results: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. Conclusion: Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active components of the FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.

Although the pathogenesis of ulcerative colitis (UC) remains elusive, substantial progress in understanding its development and progression has been achieved in the past decades, and novel effective treatment strategies have been developed. Changes in gut microbiota, environmental triggers, deregulation of immunological responses, and genetic predisposition have been identified as pathogenic key factors. There are several lines of clinical observations, which support a close connection of altered gut microbiota with the development and course of UC. Despite a plethora of microbiota alterations in UC, it is currently unclear whether the observed changes in inflammation are cause or effect of the altered microbiota state.Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore gut microbial diversity, bacterial richness, and microbial homeostasis in UC. FMT is an already established treatment option for recurrent Clostridioides difficile infection, and several case series and randomized controlled trials have described its use in UC. In this review, we evaluate recent efficacy and safety data on FMT for UC, discuss possible pitfalls and show possible areas of future development. Although FMT could become a promising treatment modality for UC, based on currently available data, FMT should be only performed in clinical trials as controlled studies focusing on long-term outcomes and safety are warranted.Das Verständnis der Colitis ulcerosa (CU) ist in den letzten Dekaden stetig gewachsen; unterschiedliche Therapiekonzepte sind für verschiedene Krankheitssituationen standardisiert. In der Pathogenese wird der gastrointestinalen Mikrobiota, Umweltfaktoren, überschießenden immunologischen Reaktionen und genetischen Faktoren eine immer größere Bedeutung zugeordnet. So zeigen zahlreiche klinische Beobachtungen eine enge Verbindung zwischen einer dysbiotischen Mikrobiota und der Erstmanifestation und dem Verlauf der CU an. Vor dem Hintergrund, dass genetische Faktoren und inflammatorische Reaktionen die Mikrobiota selber verändern können ist aber nicht klar, was Ursache und Folge ist. Der Fäkale Mikrobiom Transfer (FMT) ist der drastischste Eingriff um eine dysbiotische Mikrobiota zu normalisieren. Mittlerweile ist ein FMT eine akzeptierte Behandlung der rezidivierenden Clostridioides difficile-Infektion; zahlreiche Fallserien und kontrollierte Studien untersuchen dieses Konzept auch bei Patienten mit CU. Vor diesem Hintergrund erfolgt eine Zusammenfassung der aktuellen Literatur bezüglich Effektivität und Sicherheit. Mögliche Limitationen und offene Fragen werden diskutiert, um das Konzept des FMT zur Therapie der CU zu verbessern. Ohne Zweifel sind dringend weitere kontrollierte Studien notwendig; ein FMT sollte bei CU nicht außerhalb dieser erfolgen.

BACKGROUND Smoking worsens Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the toxicity of dioxinlike chemicals. We hypothesized that AHR variants and smoking influence CD. METHODS Exon-intron boundaries and coding and promoter regions of AHR gene were sequenced (28 patients with inflammatory bowel disease; 4 healthy controls). Two identified variants (rs7796976 and rs2066853) were studied for an association with intestinal permeability (IP, oral sugar test) in patients with inflammatory bowel disease (stratified according to the smoking status). AHR expression was analyzed by quantitative real-time polymerase chain reaction in colonic biopsies from patients with CD (n = 53). Case-control analysis including a genotype-phenotype correlation was performed for both variants (n = 767 patients with inflammatory bowel disease; n = 466 healthy controls). RESULTS Sequencing identified a putative promoter variant (rs7796976) and a nonsynonymous variant (rs2066853; Arg554Lys) in AHR, both predicted to be functionally relevant. The major G-allele of rs7796976 increased the risk for disturbed IP (odds ratio 1.9, 95% confidence interval [CI], 1.1-3.2) in CD but not ulcerative colitis. We observed an additive effect of the rs7796976 genotype and smoking on IP (P = 0.005), which was also shown for rs2066853 (P = 0.004; variants not linked). Both variants showed a genotype-dependent AHR expression in colonic biopsies of patients with CD. No overall association with either CD or ulcerative colitis was observed; however, the rs7796976 genotype and smoking increased the risk for the L4 phenotype in CD. CONCLUSION Smoking and functionally relevant AHR variants increase IP in CD. Because AhR is known to mediate between smoking and inflammation, these variants might be involved in the deleterious effect of smoking on CD.

Background The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. Methods Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. Results For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. Conclusion The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.

Osteonecrosis (ON) is characterized by an infarction of osseous tissue in the subchondral regions of the bone. We report the case of a young male patient with ulcerative colitis (UC) developing severe and multifocal, large joint ON resulting in severe disability. Since typical symptoms of ON, like joint pain, might be misinterpreted as common extraintestinal manifestations, ON might easily be overlooked in patients with inflammatory bowel disease (IBD). Plain radiographs detect only advanced cases, MRI is the diagnostic method of choice with a specificity and sensitivity of > 90 %. We discuss the incidence of ON specifically in IBD and provide an update on risk factors like treatment with corticosteroids (CS), although ON has been reported in IBD patients without previous CS treatment. Apart from that, underlying inflammation, thromboembolic events and genetic risk factors might be involved in ON development supporting the hypothesis of a complex cascade. Causative therapies for ON are not available, and surgical interventions like trepanning, core decompression and prosthetic replacement are often necessary. Our intention is to direct attention to this severe complication in the differential work-up of joint pain in IBD patients.